Trial Outcomes & Findings for Study of Changes in Estrogen Levels and Grip Strength in Postmenopausal Women Who Have Received 4 to 6 Years of Hormone Therapy for Breast Cancer and Are Currently Receiving Letrozole on Clinical Trial IBCSG-35-07 (NCT NCT01281137)

Last Updated: 2021-10-06

Results Overview

In SOLE-EST, levels of E1, E2, and E1S were summarized over time at 0 (baseline), 9, 10.5, and 12 months from randomization among patients in the longitudinal analysis population (N=90 with post-baseline sample).

Recruitment status

COMPLETED

Target enrollment

104 participants

Primary outcome timeframe

0 (baseline), 9, 10.5, and 12 months from randomization

Results posted on

2021-10-06

Participant Flow

The phase 3 randomized, open-label Study of Letrozole Extension (SOLE) enrolled 4884 postmenopausal women between December 2007 and October 2012. Among them, 104 patients were enrolled in the SOLE Estrogen Substudy (SOLE-EST). SOLE was a multinational study performed in 240 centers of the Breast International Group-affiliated cooperative groups in 22 countries.

There were 104 patients enrolled during the active period (25 continuous letrozole, 79 intermittent letrozole). Blood samples were obtained from 103 patients at baseline. For the longitudinal analysis, patients (N=90) were included if they had at least one post-baseline sample. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent) and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in longitudinal analyses.

Participant milestones

Participant milestones
Measure	Continuous Letrozole Treatment Group The phase 3 randomized, open-label Study of Letrozole Extension (SOLE) enrolled 4884 postmenopausal women between December 2007 and October 2012. Among them, 104 patients were enrolled in the SOLE Estrogen Substudy (SOLE-EST).Patients were randomized 1:1 for SOLE and enrolled in 1:3 ratio for SOLE-EST between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3 month interruption in years 1-4 and then 2.5 mg/day during all year 5).	Intermittent Letrozole Treatment Group The phase 3 randomized, open-label Study of Letrozole Extension (SOLE) enrolled 4884 postmenopausal women between December 2007 and October 2012. Among them, 104 patients were enrolled in the SOLE Estrogen Substudy (SOLE-EST).Patients were randomized 1:1 for SOLE and enrolled in 1:3 ratio for SOLE-EST between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3 month interruption in years 1-4 and then 2.5 mg/day during all year 5).
Baseline Population STARTED	25	79
Baseline Population COMPLETED	25	78
Baseline Population NOT COMPLETED	0	1
Analysis Population (Baseline) STARTED	25	78
Analysis Population (Baseline) COMPLETED	21	69
Analysis Population (Baseline) NOT COMPLETED	4	9
Analysis Population (9 Months) STARTED	21	69
Analysis Population (9 Months) COMPLETED	21	64
Analysis Population (9 Months) NOT COMPLETED	0	5
Analysis Population (10.5 Months) STARTED	21	64
Analysis Population (10.5 Months) COMPLETED	20	64
Analysis Population (10.5 Months) NOT COMPLETED	1	0
Analysis Population (12 Months) STARTED	20	64
Analysis Population (12 Months) COMPLETED	19	62
Analysis Population (12 Months) NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Continuous Letrozole Treatment Group The phase 3 randomized, open-label Study of Letrozole Extension (SOLE) enrolled 4884 postmenopausal women between December 2007 and October 2012. Among them, 104 patients were enrolled in the SOLE Estrogen Substudy (SOLE-EST).Patients were randomized 1:1 for SOLE and enrolled in 1:3 ratio for SOLE-EST between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3 month interruption in years 1-4 and then 2.5 mg/day during all year 5).	Intermittent Letrozole Treatment Group The phase 3 randomized, open-label Study of Letrozole Extension (SOLE) enrolled 4884 postmenopausal women between December 2007 and October 2012. Among them, 104 patients were enrolled in the SOLE Estrogen Substudy (SOLE-EST).Patients were randomized 1:1 for SOLE and enrolled in 1:3 ratio for SOLE-EST between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3 month interruption in years 1-4 and then 2.5 mg/day during all year 5).
Baseline Population No samples assayed (excluded from all analyses)	0	1
Analysis Population (Baseline) baseline sample only so excluded from longitudinal analysis	4	9
Analysis Population (9 Months) 5 from the baseline analysis population did not have samples assayed for the analysis at month 9.	0	5
Analysis Population (10.5 Months) 1 from the baseline analysis population did not have a sample assayed for analysis at month 10.5	1	0
Analysis Population (12 Months) 3 from the baseline analysis population did not have a sample assayed for analysis at month 12	1	2

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Continuous Letrozole Treatment Group n=25 Participants Patients were randomized 1:1 for SOLE and enrolled in 1:3 ratio for SOLE-EST between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3 month interruption in years 1-4 and then 2.5 mg/day during all year 5).	Intermittent Letrozole Treatment Group n=78 Participants Patients were randomized 1:1 for SOLE and enrolled in 1:3 ratio for SOLE-EST between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3 month interruption in years 1-4 and then 2.5 mg/day during all year 5).	Total n=103 Participants Total of all reporting groups
Age, Customized Age at randomization, years · <55	6 Participants n=25 Participants	23 Participants n=78 Participants	29 Participants n=103 Participants
Age, Customized Age at randomization, years · 55-59	6 Participants n=25 Participants	13 Participants n=78 Participants	19 Participants n=103 Participants
Age, Customized Age at randomization, years · 60-64	3 Participants n=25 Participants	15 Participants n=78 Participants	18 Participants n=103 Participants
Age, Customized Age at randomization, years · 65-69	5 Participants n=25 Participants	12 Participants n=78 Participants	17 Participants n=103 Participants
Age, Customized Age at randomization, years · ≥70	5 Participants n=25 Participants	15 Participants n=78 Participants	20 Participants n=103 Participants
Sex: Female, Male Female	25 Participants n=25 Participants	78 Participants n=78 Participants	103 Participants n=103 Participants
Sex: Female, Male Male	0 Participants n=25 Participants	0 Participants n=78 Participants	0 Participants n=103 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Body Mass Index (BMI) at randomization Normal (<25)	12 Participants n=25 Participants	27 Participants n=78 Participants	39 Participants n=103 Participants
Body Mass Index (BMI) at randomization Overweight (25-<30)	7 Participants n=25 Participants	31 Participants n=78 Participants	38 Participants n=103 Participants
Body Mass Index (BMI) at randomization Obese (≥30)	6 Participants n=25 Participants	20 Participants n=78 Participants	26 Participants n=103 Participants
Body Mass Index (BMI) at randomization Unknown	0 Participants n=25 Participants	0 Participants n=78 Participants	0 Participants n=103 Participants
Type of menopause Bilateral oophorectomy	4 Participants n=25 Participants	22 Participants n=78 Participants	26 Participants n=103 Participants
Type of menopause Chemotherapy-induced amenorrhea	7 Participants n=25 Participants	8 Participants n=78 Participants	15 Participants n=103 Participants
Type of menopause Natural menopause before breast cancer diagnosis	13 Participants n=25 Participants	41 Participants n=78 Participants	54 Participants n=103 Participants
Type of menopause Natural menopause since breast cancer diagnosis	1 Participants n=25 Participants	7 Participants n=78 Participants	8 Participants n=103 Participants
Last (most recent) type of prior endocrine therapy (ET) Aromatase inhibitor (AI)	23 Participants n=25 Participants	72 Participants n=78 Participants	95 Participants n=103 Participants
Last (most recent) type of prior endocrine therapy (ET) Selective estrogen receptor modulators (SERM)	2 Participants n=25 Participants	6 Participants n=78 Participants	8 Participants n=103 Participants
Duration of prior AI <6 months	2 Participants n=25 Participants	5 Participants n=78 Participants	7 Participants n=103 Participants
Duration of prior AI 6 months - <2 years	0 Participants n=25 Participants	3 Participants n=78 Participants	3 Participants n=103 Participants
Duration of prior AI 2 - <3 years	5 Participants n=25 Participants	14 Participants n=78 Participants	19 Participants n=103 Participants
Duration of prior AI 3 - <4 years	3 Participants n=25 Participants	10 Participants n=78 Participants	13 Participants n=103 Participants
Duration of prior AI ≥4 years	15 Participants n=25 Participants	46 Participants n=78 Participants	61 Participants n=103 Participants
Duration of prior AI Unknown	0 Participants n=25 Participants	0 Participants n=78 Participants	0 Participants n=103 Participants
Duration from end of prior ET to randomization ≤ 1 month	20 Participants n=25 Participants	61 Participants n=78 Participants	81 Participants n=103 Participants
Duration from end of prior ET to randomization >1 month	5 Participants n=25 Participants	17 Participants n=78 Participants	22 Participants n=103 Participants

PRIMARY outcome

Timeframe: 0 (baseline), 9, 10.5, and 12 months from randomization

Population: Longitudinal analysis group: There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85, 84, and 81, respectively, could be included in analyses of hormone levels over time.

Outcome measures

Outcome measures
Measure	Continuous Letrozole Treatment Group (Baseline, Month 0) n=21 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (Baseline, Month 0) n=69 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (9 Months) n=21 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (9 Months) n=64 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (10.5 Months) n=20 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (10.5 Months) n=64 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (12 Months) n=19 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (12 Months) n=62 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.
Levels of Estrone (E1), Estradiol (E2), and Estrone Sulphate (E1S) Among Patients in the Longitudinal Analysis Population E1	12.4 pg/mL Interval 9.7 to 23.4	14.3 pg/mL Interval 5.8 to 26.1	4.8 pg/mL Interval 4.2 to 5.5	5.1 pg/mL Interval 4.3 to 5.8	4.7 pg/mL Interval 3.9 to 5.5	21.6 pg/mL Interval 15.4 to 29.7	5.1 pg/mL Interval 4.4 to 7.0	26.8 pg/mL Interval 18.5 to 35.7
Levels of Estrone (E1), Estradiol (E2), and Estrone Sulphate (E1S) Among Patients in the Longitudinal Analysis Population E2	4.6 pg/mL Interval 3.3 to 7.3	4.7 pg/mL Interval 3.4 to 6.9	2.6 pg/mL Interval 2.2 to 4.0	3.2 pg/mL Interval 2.4 to 4.0	2.6 pg/mL Interval 2.0 to 3.7	6.7 pg/mL Interval 4.8 to 8.7	2.9 pg/mL Interval 2.3 to 4.0	7.3 pg/mL Interval 5.4 to 10.5
Levels of Estrone (E1), Estradiol (E2), and Estrone Sulphate (E1S) Among Patients in the Longitudinal Analysis Population E1S	90.7 pg/mL Interval 75.2 to 150.2	87.6 pg/mL Interval 58.1 to 142.3	61.1 pg/mL Interval 50.5 to 76.2	54.1 pg/mL Interval 47.8 to 63.0	57.1 pg/mL Interval 50.6 to 69.0	128.6 pg/mL Interval 90.7 to 156.8	59.1 pg/mL Interval 47.3 to 73.5	125.1 pg/mL Interval 93.0 to 188.2

PRIMARY outcome

Timeframe: 9, 10.5, and 12 months from baseline

Population: Longitudinal Analysis Population: There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. 90 patients at baseline, 85 patients at month 9, 84 patients at month 10.5, and 81 patients at month 12.

Changes in hormone levels (E1, E2, and E1S levels), as percentage change over time according to treatment assignment (at 9, 10.5 and 12 months from baseline).

Outcome measures

Outcome measures
Measure	Continuous Letrozole Treatment Group (Baseline, Month 0) n=21 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (Baseline, Month 0) n=64 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (9 Months) n=20 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (9 Months) n=64 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (10.5 Months) n=19 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (10.5 Months) n=62 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (12 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (12 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.
Percent Change of E1, E2, and E1S Levels at 9, 10.5, and 12 Months From Baseline, by Treatment Group Percent change of E1	-58.2 percentage change Interval -77.2 to -44.9	-59.3 percentage change Interval -79.4 to -13.9	-67.3 percentage change Interval -81.1 to -53.0	76.6 percentage change Interval -22.7 to 289.3	-57.8 percentage change Interval -75.4 to -34.8	68.7 percentage change Interval -14.4 to 318.9	—	—
Percent Change of E1, E2, and E1S Levels at 9, 10.5, and 12 Months From Baseline, by Treatment Group Percent change of E2	-34.2 percentage change Interval -59.2 to -10.6	-32.2 percentage change Interval -58.9 to -2.8	-39.6 percentage change Interval -56.9 to -11.1	62.7 percentage change Interval -18.1 to 111.3	-47.7 percentage change Interval -60.5 to 0.2	46.2 percentage change Interval -12.1 to 118.3	—	—
Percent Change of E1, E2, and E1S Levels at 9, 10.5, and 12 Months From Baseline, by Treatment Group Percent change of ES1	-29.8 percentage change Interval -60.9 to -15.3	-42.3 percentage change Interval -62.2 to -7.9	-38.7 percentage change Interval -63.4 to -22.6	32.9 percentage change Interval -20.3 to 96.7	-36.7 percentage change Interval -68.5 to -21.5	31.6 percentage change Interval -2.4 to 103.1	—	—

SECONDARY outcome

Timeframe: 6 and 12 months

Population: In total, 76/85 patients (19 continuous; 57 intermittent) who had a 9 month sample also had a sample at 12 months and are included in analyses relating E2 change (9 to 12m) with QL, grip strength and adverse event (AE) changes.

Toxicity grade changes from 6 to 12 months (hot flashes, insomnia and arthralgia; Common Terminology Criteria for Adverse Events (CTCAE) version 3 values 1- 4 grouped as no change, increase in grade \[worsening\] or decrease in grade \[improvement\])

Outcome measures

Outcome measures
Measure	Continuous Letrozole Treatment Group (Baseline, Month 0) n=19 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (Baseline, Month 0) n=57 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (9 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (9 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (10.5 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (10.5 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (12 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (12 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.
Toxicity Grade Changes for Arthralgia, Hot Flushes, and Insomnia AE: Hot Flushes Grade Change from 6 to 12 Months	0.0 toxicity grade Interval 0.0 to 0.0	0.0 toxicity grade Interval 0.0 to 0.0	—	—	—	—	—	—
Toxicity Grade Changes for Arthralgia, Hot Flushes, and Insomnia AE: Insomnia Grade Change from 6 to 12 Months	0.0 toxicity grade Interval 0.0 to 0.0	0.0 toxicity grade Interval 0.0 to 0.0	—	—	—	—	—	—
Toxicity Grade Changes for Arthralgia, Hot Flushes, and Insomnia AE: Arthralgia Grade Change from 6 to 12 Months	0.0 toxicity grade Interval 0.0 to 0.0	0.0 toxicity grade Interval 0.0 to 0.0	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 6 and 12 months: Change is calculated from 12 months minus 6 months, therefore positive values indicate an improved condition and negative values indicate a declined condition

Population: In total, 76/85 patients (19 continuous; 57 intermittent) who had a 6 month sample also had a sample at 12 months and are included in analyses relating E2 change (6 to 12m) with QL, grip strength and AE changes.

All patients in SOLE-EST were assessed for symptom specific QoL. QoL changes from 6 to 12 months (sleep change, hot flushes, tiredness, difficulties of becoming aroused, loss of sexual interest, physical wellbeing and mood; LASA (linear analogue self-assessment) scores 0-100 (higher is better QoL) were calculated as 12 months minus 6 months, so that negative is worsening and positive is improvement.

Outcome measures

Outcome measures
Measure	Continuous Letrozole Treatment Group (Baseline, Month 0) n=19 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (Baseline, Month 0) n=57 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (9 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (9 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (10.5 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (10.5 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (12 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (12 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.
Quality of Life (QoL) Score Changes LASA sleep disturbance score change from 12 to 6 months	0.0 score on a scale Interval -6.5 to 14.5	-9.5 score on a scale Interval -27.0 to 2.0	—	—	—	—	—	—
Quality of Life (QoL) Score Changes LASA hot flush score change from 12 to 6 months	2.0 score on a scale Interval -3.0 to 12.0	-2.0 score on a scale Interval -13.0 to 6.0	—	—	—	—	—	—
Quality of Life (QoL) Score Changes LASA tiredness score change from 12 to 6 months	-1.0 score on a scale Interval -19.0 to 7.0	-9.0 score on a scale Interval -23.0 to 3.0	—	—	—	—	—	—
Quality of Life (QoL) Score Changes LASA difficulty becoming aroused score change from 12 to 6 months	0.5 score on a scale Interval -7.5 to 20.5	0.0 score on a scale Interval -16.0 to 3.0	—	—	—	—	—	—
Quality of Life (QoL) Score Changes LASA loss of sexual interest score change from 12 to 6 months	-3.0 score on a scale Interval -18.0 to 8.0	-1.5 score on a scale Interval -8.5 to 4.5	—	—	—	—	—	—
Quality of Life (QoL) Score Changes LASA physical well-being score change from 12 to 6 months	-1.0 score on a scale Interval -13.5 to 5.5	-5.0 score on a scale Interval -19.0 to 12.0	—	—	—	—	—	—
Quality of Life (QoL) Score Changes LASA mood score change from 12 to 6 months	0.0 score on a scale Interval -3.0 to 7.0	-1.0 score on a scale Interval -24.0 to 10.0	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Changes in grip strength score is calculated at 12 months minus 9 months

Population: Longitudinal analysis population N=90 (21 Continuous letrozole; 69 Intermittent letrozole); N samples per timepoint: N=90 at baseline, N=85 at month 9; N= 84 at month 10.5, N=81 at month 12. In total, 76/85 patients (19 continuous; 57 intermittent) who had a 9 month sample also had a sample at 12 months and are included in analyses relating E2 change (9 to 12m) with grip strength.

Grip strength was measured using the Martin Vigorimeter (a modified sphygmomanometer which measures the force of compression in kilo pascal by means of a compressible rubber ball). To perform the hand grip test, the patients were asked to squeeze the ball of a modified sphygmomanometer three times with maximal force and the maximal value of three trials of each hand were used for evaluation. Higher value represents greater strength, thus changes are calculated as 12 months minus 9 months so that positive is improved condition and negative is declined condition.

Outcome measures

Outcome measures
Measure	Continuous Letrozole Treatment Group (Baseline, Month 0) n=19 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (Baseline, Month 0) n=57 Participants There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (9 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (9 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (10.5 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (10.5 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Continuous Letrozole Treatment Group (12 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.	Intermittent Letrozole Treatment Group (12 Months) There were 90/103 patients (21 continuous, 69 intermittent) who had baseline and one or more samples at 9, 10.5 and/or 12 months and could be included in analyses of hormone levels over time. At 9, 10.5, and 12 months, 85 (21 continuous, 64 intermittent), 84 (20 continuous, 64 intermittent), and 81 (19 continuous, 62 intermittent), patients, respectively, could be included in analyses of hormone levels over time.
Change in Grip-strength Score in the Dominant Hand	-1.0 kilopascals Interval -6.0 to 2.0	0.0 kilopascals Interval -6.0 to 4.0	—	—	—	—	—	—

Adverse Events

Continuous Letrozole Treatment Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Intermittent Letrozole Treatment Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Head Trial Activities and Deputy Director: Dr. Heidi Roschitzki-Voser

International Breast Cancer Study Group (IBCSG)

Phone: +41 31 511 94 00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place